Pictured: Dr. Weihong Song (left) with Dr. Yun Zhang (right), co-first author on the paper described below. Image credit: Paul Joseph/UBC.
Can a protein that protects the brain from stroke damage indicate Alzheimer disease (AD)? New research from Dr. Weihong Song and colleagues recently found the first evidence of a direct interaction between macrophage migration inhibitory factor (MIF), a protein that is both inflammatory and neuroprotective, and amyloid-beta protein (Aβ), the main component in plaque in the AD brain. These findings suggest the possibility of a biomarker for AD.
The study, published recently in the journal Alzheimer’s Research & Therapy, offered new clarity on the role of MIF in maintaining cognitive function during the early stages of AD and protecting against brain cell death.
Inflammation is an important function of healing after injury or infection, and the proteins responsible for inflammation can be beneficial in regulated amounts, providing protection to vulnerable tissues and cells. However, when these proteins are improperly regulated and occur in excess, they pose a risk to the health of those same tissues and cells. When MIF functions normally, it regulates immune function. MIF has been detected in Aβ plaques in postmortem brain tissue. The study showed that neurons secrete MIF in response to Aβ, and inadequate production of MIF in the central nervous system (CNS) contributes to neurodegeneration.
“Using Alzheimer’s mouse models, we can see that MIF seems to be playing a protective role in reducing Aβ-induced neurotoxicity,” said Dr. Song. “When MIF level is reduced by disrupting its gene expression, cognitive decline was accelerated in AD mice.”
The effects of MIF seem to be related to AD and not to other forms of dementia.
“Our findings suggest that MIF may act as a defense mechanism in individuals developing AD, and that increased MIF in the blood or cerebral spinal fluid may be a biomarker for AD,” said Dr. Song.
In 2014, Dr. Song and colleagues found that lower level of MIF contributed to accelerating neuron death during stroke; the study at the time found that inhibiting MIF expression could contribute to a higher risk of damage post-stroke. In balance, MIF appeared to moderate inflammation, activate cell survival signals, and protect against cell death following an ischemic event.
“When MIF is doing what it is supposed to do, it may prevent neurodegeneration,” explained Dr. Song. “When it is overexpressed, it may make a viable diagnostic marker for AD; our data provides first-hand evidence of how MIF is expressed in AD, and its effect on disease progression.”
For Dr. Song and colleagues, the next step will be to evaluate MIF signaling and determine whether neurodegeneration can be inhibited while maintaining the protective function of the protein.